Questions people actually ask · Glossary
J147: straight answers, including the ones that are “nobody knows”
Several of these answers are unsatisfying. They are unsatisfying because the evidence is, and an answer that sounds better than the evidence is worth nothing to anyone.
What is J147?
A synthetic small molecule derived from curcumin, developed at the Salk Institute by phenotypic screening against old-age-associated brain toxicities. Its molecular target is ATP5A, the alpha subunit of mitochondrial F1-ATP synthase. It is an investigational research compound and is not an approved medicine anywhere.
How is J147 different from curcumin?
Chemically: it replaces curcumin's β-diketone linker — which tautomerises and hydrolyses readily — with a stable pyrazole-linked hydrazide scaffold, keeping the aromatic ends. Biologically: it is neurotrophic in assays where curcumin is inactive, and is more stable and more bioavailable. Curcumin was the starting point, not the medicine.
What is the best synthesis route for J147?
The published routes are convergent and short: aromatic fragments prepared separately, joined through the heterocyclic linker. The difficulty is not making the molecule but making it reproducibly clean — which is a question of impurity profile, residual solvent and solid-state form rather than of yield. Our synthetic work runs on SYNTHESERACT, our own platform, so the impurity profile is generated in-house rather than inherited on a certificate. Full chemistry page.
Has J147 been tested in humans?
Once. NCT03838185 — a Phase 1 randomised, double-blind, placebo-controlled study of single ascending oral doses in 64 healthy young and elderly volunteers, sponsored by Abrexa Pharmaceuticals. It ran from January 2019 to February 2020 and is recorded as completed. No results have been posted and no publication of the outcome was found. No later-phase trial is registered.
Is J147 safe?
Nobody can answer that from the public record. J147 completed the animal toxicology required to enter human trials, and a Phase 1 safety study was completed — but its results were never published. An unpublished safety study is not evidence of safety, and it is not evidence of harm. It is an absence.
What is the dose of J147?
There is no established human dose. Published mouse work spans roughly 1–200 mg/kg/day orally, with dietary supplementation at 200 ppm appearing in the literature. Animal doses do not convert to human doses by arithmetic. This site gives no dosing advice.
Where can I buy J147?
It is sold by chemical suppliers as a research compound. Nothing is supplied from this site for human use. If you are sourcing material for research, the questions worth asking are: identity by NMR and mass spectrometry; a named impurity profile rather than one purity percentage; residual solvent; and solid-state form. Those four decide whether your experiment means anything.
Is J147 a nootropic?
It is often described that way online. The published work is about neuroprotection, synaptic protein preservation and memory in ageing and disease models in animals — not cognitive enhancement in healthy humans, on which there is no evidence at all.
What is the difference between J147, CAD-031 and CMS121?
Three different compounds. J147 is the curcumin-derived compound with the ATP5A target. CAD-031 is a separate compound derived from J147. CMS121 is a fisetin derivative from a different lineage, which has been through a Phase 1 of its own reported in a 2025 preprint. Some secondary sources print J147 and CAD-031 as one compound. They are not.
Has J147 been studied in autism?
No — not in any language, in any model. We searched for it specifically and found nothing. The autism page says what the mechanisms suggest, states plainly that nobody has tested it, and sets out what an honest first experiment would look like.
Why has J147 not progressed further?
The public record does not say. What it shows is a completed Phase 1 whose results were never posted or published, and no registered later-phase trial. Anything beyond that would be speculation, and we are not going to dress speculation up as an explanation.
Glossary
- ATP synthase
- The enzyme at the end of oxidative phosphorylation that makes ATP, the cell's energy currency. It sits in the inner mitochondrial membrane and works as a rotary motor driven by proton flow.
- ATP5A
- The alpha subunit of the F1 head of mitochondrial ATP synthase — the specific protein identified as J147's molecular target in 2018.
- AMPK
- AMP-activated protein kinase, a central cellular energy sensor. It is switched on when energy is scarce and coordinates the response.
- CAMKK2
- A calcium/calmodulin-dependent kinase that sits upstream of AMPK — one of the routes by which a change in calcium handling becomes a change in energy signalling.
- BDNF · NGF
- Brain-derived neurotrophic factor and nerve growth factor: proteins that support the survival, growth and connection of neurons. “Neurotrophic” describes compounds that promote this kind of signalling.
- Phenotypic screening
- Selecting compounds by what they do to cells or organisms rather than by whether they hit a chosen target. It finds things a target hypothesis would never propose — at the cost of not knowing, at first, what you have found.
- TLR4 / NF-κB
- Toll-like receptor 4 and the transcription factor it signals through: a principal route by which microglia, the brain's immune cells, mount an inflammatory response.
- Oral bioavailability
- The fraction of an oral dose that reaches systemic circulation intact. J147's is about 28 % in mice, which means roughly seven-tenths of an oral dose never becomes exposure.
- Half-life (t½)
- The time for concentration to fall by half. J147's is about 1.5 hours in plasma and 2.5 hours in brain, in mice — a short window, which is why the dosage form matters so much.
- Brain-to-blood ratio
- How much of a compound is in brain tissue relative to blood. J147's is around 0.5: it crosses the blood–brain barrier readily and does not accumulate.
- Lyophilisation
- Freeze-drying: removing water by sublimation from the frozen state to leave a dry cake that is reconstituted before use. It is how unstable material is made storable.
- Phase 1
- The first stage of human testing, in a small group, assessing safety, tolerability and pharmacokinetics — not whether the compound works.
- Freedom to operate
- Whether a planned commercial activity can proceed without infringing patents in force in a given territory. It is a legal assessment, produced by qualified people, and nothing on this site substitutes for one.
Research use only
J147 is an investigational compound. It is not approved as a medicine in any territory, it is not supplied here for human use, and nothing on this page is dosing advice. Nothing here is medical advice.
